The leading causes of FHF are viral hepatitis and hepatotoxic drug reactions. Although viral hepatitis can lead to liver failure, fewer than 5% of patients with viral hepatitis actually develop it. Other causes include chronic alcohol abuse, hepatotoxic drug reactions (acetominophen in particular), acute infection or hemorrhage that leads to shock, prolonged cholestasis (arrest of bile excretion), and metabolic disorders. Many of these lead to cirrhosis, a chronic liver disease that results in widespread tissue fibrosis, nodule formation, and necrosis of the liver tissue.

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